Ion suppression is one form of matrix effect that liquid chromatography–mass spectrometry (LC–MS) techniques suffer from, regardless of the sensitivity or selectivity of the mass analyzer used. Ion suppression negatively affects several analytical figures of merit, such as detection capability, precision, and accuracy. The limited knowledge of the origin and mechanism of ion suppression makes this problem difficult to solve in many cases. Over the past decade and a half since the response-reducing phenomenon was exposed, however, protocols have been developed not only to test for its presence but also to account for its effects and eliminate the risk of ion suppression altogether. Because there is no universal solution for the matrix effect, some of the viable options are discussed briefly in this tutorial, which alone or in combination can help regain the quality of LC–MS analysis for the particular matrix–analyte combination. Two commonly used techniques to detect the presence of the matrix effect are illustrated. Modifying instrumental components and parameters, chromatographic separation, and sample preparation are all considered as means of reducing or possibly eliminating ion suppression. A variety of calibration techniques for compensating the effects of the phenomenon also are discussed.